This proposal describes proposed studies for the continuation of the Soft Tissue Sarcoma (STS) Program Project, CA47179. We have continued the overall original objectives of designing and implementing a comprehensive and integrated multi-disciplinary program approach to the biology, pathogenesis and natural history of Soft Tissue Sarcoma (STS) Program Project, CA47179. We have continued the overall original objectives of designing and implementing a comprehensive and integrated multi-disciplinary program approach to the biology, pathogenesis and natural history of soft tissue sarcoma with the goal to translate this information into improve treatment of STS. Thus, our research program on the molecular genetic and biological characteristics of STS is geared to the development of novel therapeutic strategies and agents. A major unique resource of our program is the patient population: over the past 15 years, 3796 adult patients with STS have been admitted to MSKC. We continue and plan to expand the maintenance of the prospective clinical database on this population. In this revised renewal application, based on our accomplishments we have designed 4 projects to expand and explore new directions in the biology of STS and its application to the clinic. In Project, Clinical Studies, we have refined our efforts our efforts using regional lung perfusion to deliver potentially therapeutic agents to patients with metastatic lung disease as well as to continue an integrated preclinical/clinical immunotherapy program aimed at the effective delivery of tumor vaccines. In Project, based on previous studies, we continue the study of functional and immunophenotypic analysis of p53 and Rb pathways. In Project, studies continue our biochemical and molecular characterization of drug resistance with initial efforts of its translation into the design of clinical trials. In Project, a new initiative, we plan a project on defining the molecular genetics on synovial sarcoma and its impact on prognosis and gene expression. These 4 projects are supported by 3 Cores: Administrative/Clinical, pathology and Biostatistics.